PATHOLOGY OF THE LIVER

CHOLESTASIS• Systemic retention of bilirubin and other solutes

eliminated in bile (e.g. bile salts & cholesterol).

• Results from hepatocellular dysfunction & (intra-or extrahepatic) biliary obstruction .

• c/p: Jaundice, pruritis, skin xanthomas, malabs.

• Lab: Elevated bilirubin, alk. phosphatase, lipids .

• Bx: bile pigment accumulation, foamy degenerat-ion, bile duct distension & proliferation, bile lakes, portal tract fibrosis, hepatocytes degeneration and necrosis , cholangitis & cholangiolitis .

• Types:

– Intrahepatic

– Extrahepatic

PATHOLOGY OF

CHOLESTASIS

1. Accumulation of bile pigment within hepatic parenchyma

2. Hepatocyte swelling and foamy degeneration & necrosis .

3. Bile duct proliferation secondary to biliary tree

obstruction

4. Hepatocyte necrosis, bile lakes, & portal tract fibrosis

PEDIATRIC LIVER DISEASES

NEONATAL CHOLESTASIS• Prolonged conjugated hyperbilirubinemia in the newborn

• Major causes: EHBA & neonatal hepatitis

– Bile duct obstruction: Extrahepatic biliary atresia(EHBA)

– Neonatal infections: CMV, sepsis, UTI, syphilis

– Toxic: drugs, parenteral nutrition

– Metabolic diseases: tyrosinemia, Niemann-Pick disease, galactosemia, AAT deficiency, cystic fibrosis, ..

– Miscellaneous: shock, hypoperfusion, Alagille’ssyndrome (paucity of bile ducts), ..

– Idiopathic neonatal hepatitis

PEDIATRIC LIVER DISEASES

NEONATAL CHOLESTASIS

• Clinical presentation is typical: jaundice, dark urine, light stools, hepatomegaly

• Neonatal hepatitis may be primary (idiopathic) or secondary

1. Idiopathic neonatal hepatitis (50-60%).

2. Extrahepatic biliary atresia (20%) .

3. AAT deficiency (15%) .

• Distinction between these disorders is essential because management is different

• Liver biopsy is important in the diagnosis

HEPATIC FAILURE• Mostly due to progressive, or less often sudden

massive hepatic destruction with erosion of 80-90% of hepatic functional capacity .

• Causes:– 1) Chronic liver disease (acute or chronic failure):

chronic active hepatitis and most types of cirrhosis

– 2) Massive hepatic necrosis (fulminant failure): viral hepatitis, drug & chemical toxicity (acetaminophen, halothane, rifampicin, INH, MOI antidepressants, CCl4, Amanita mushroom toxins

– 3) Hepatic dysfunction without overt necrosis: viable but nonfunctional hepatocytes, e.g. Reye’s syndrome,

tetracycline toxicity, acute fatty liver of pregnancy .

. Clinical Consequences of Liver Disease

Characteristic signs Hepatic dysfunction:

•Jaundice and cholestasis

•Hypoalbuminemia

•Hyperammonemia

•Hypoglycemia

•Fetor hepaticus

•Palmar erythema

•Spider angiomas

•Hypogonadism

•Gynecomastia

•Weight loss

•Muscle wasting

Portal hypertension from cirrhosis:

•Ascites

•Splenomegaly

•Hemorrhoids

•Caput medusae-abdominal skin

Life-threatening

complications •Hepatic failure

•Multiple organ failure

•Coagulopathy

•Hepatic encephalopathy

•Hepatorenal syndrome

•Portal hypertension from cirrhosis

•Esophageal varices, risk of

rupture

•Malignancy with chronic disease

•Hepatocellular carcinoma

HEPATIC FAILURE

• Most cases are due to overwhelming viral hepatitis and alcoholic liver disease .

• Symptoms may occur within days with or without prior history of liver disease .

• A variety of stressful events may contribute to onset of failure:

– GI bleeding

– Acute infections

– Electrolyte disturbances

– Major surgery, heart failure, shock

• Treatment: not satisfactory

• Px: 80% mortality rate

HEPATIC ENCEPHALOPATHY• A metabolic disorder of CNS & neuromuscular

system associated with severe loss of hepatocellular function & portosystemic shunting

• The brain is exposed to an altered metabolic environment (ammonia?) which impairs neuronal function & promotes generalized brain edema .

• Patients exhibit a wide range of disturbances of consciousness: subtle behavioural changes, confusion, stupor, deep coma & death .

• Other neurologic signs: Rigidity, hyperreflexia, EEG changes, seizures, asterixis

• Minor morphologic changes in brain

HEPATO-RENAL SYNDROME

• Development of renal failure in patients with severe liver disease, without presence of intrinsic morphologic or functional causes in the kidney.

• Excluded are cases of concomitant damage to liver & kidneys and acute tubular necrosis secondary to circulatory collapse .

• Pathogenesis: due to Vascular collapse and decreased renal blood flow ?

• c/p: decrease in urine output .

• Retained ability to concentrate urine . Hyperosmolar urine, protein -ve & low Na

+ .

• Lab: Increased blood urea and creatinin .

• Px: May hasten death or may persist for months

CIRRHOSIS

• Irreversible end stage of chronic liver disease,

which leads to parenchymal injury and fibrosis

• 3 histologic features:

1. Disruption of entire liver architecture

2. Bridging fibrous septa

3. Parenchymal nodules

ETIOLOGIC CLASSIFICATION OF

CIRRHOSIS1. Viral hepatitis

2. Alcoholic liver disease

3. Biliary diseases

4. Genetic hemochromatosis

5. Wilson’s disease

6. a1-antitrypsin deficiency

7. Drugs (a-methyldopa, acetaminophen…)

8. Syphilis

9. Galactosemia, tyrosinosis..

10. “Cardiac cirrhosis”

11.Cryptogenic cirrhosis